Protease-resistant peptide design-empowering nature's fragile warriors against HIV

• Published in: Biopolymers Vol. 98; no. 5; pp. 431 - 442
• Main Authors: Weinstock, Matthew T., Francis, J. Nicholas, Redman, Joseph S., Kay, Michael S.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 2012
• Subjects: Amino Acids - chemistry; Drug Design; HIV; HIV entry; HIV Envelope Protein gp41 - chemistry; HIV Fusion Inhibitors - chemistry; HIV Fusion Inhibitors - pharmacology; HIV Infections - drug therapy; HIV Infections - virology; HIV Protease Inhibitors - chemistry; HIV Protease Inhibitors - pharmacology; Humans; peptide design; Peptide Hydrolases - chemistry; Peptide Hydrolases - pharmacology; Peptide Library; Peptides - chemical synthesis; Peptides - chemistry; Peptides - pharmacology; peptidomimetics; Peptidomimetics - chemical synthesis; Peptidomimetics - chemistry; Peptidomimetics - pharmacology; Virus Internalization - drug effects
• ISSN: 0006-3525; 1097-0282
• DOI: 10.1002/bip.22073

Peptides have great potential as therapeutic agents, but their use is often limited by susceptibility to proteolysis and their resulting in vivo fragility. In this review, we focus on peptidomimetic approaches to produce protease‐resistant peptides with the potential for greatly improved clinical utility. We focus on the use of mirror‐image (D‐peptide) and ß‐peptides as two leading approaches with distinct design principles and challenges. Application to the important and difficult problem of inhibiting HIV entry illustrates the current state‐of‐the‐art in peptidomimetic technologies. We also summarize future directions for this field and highlight remaining obstacles to widespread use of protease‐resistant peptides. © 2012 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 98: 431–442, 2012.